Oxidative changes of lens proteins are thought to occur with aging and to contribute to the development of cataracts. The goals of this project are to determine (1) the extent of oxidative modification of crystallins and metabolic enzymes in both normal and cataractous lenses, (2) the nature of the modifications and mechanisms leading to the changes, and (3) the effect of the modifications on the structure and function of lens proteins. Bovine and rat lenses are used. The approach is to study the modifications of lens proteins after treatment in vitro by metal-catalyzed oxidation systems. Structural alterations induced by these oxidative systems were examined by circular dichroism and peptide mapping. Trace metal analysis of bovine aqueous and rat and bovine lenses indicated that copper and iron are both present in micromolar concentrations. Further studies on fetal bovine lenses demonstrated that copper and iron are not associated with any crystallin to an appreciable extent in vivo. In vitro, copper appears to interact specifically with some of the bovine gamma-crystallins and at greater than stoichiometric levels induces protein aggregation. These results support the possibility that metal-catalyzed oxidative reactions may contribute to age-related changes in lens.